Vacuum filter device

ABSTRACT

A vacuum filter device is disclosed which includes a filter body which is adapted to receive in fluid-fight, sealed relationship a pair of closed containers for solutions to be filtered by a membrane filter positioned within the filter body. A vacuum port in the filter body communicates with the downstream side of the membrane and a venting passageway also located in the filter body communicates with the closed sample container to serve as a vent to atmospheric pressure. The venting passageway is made of an air permeable hydrophobic filter or preferably a small enough opening to prevent the sample solutions from leaking out of the device during normal use.

BACKGROUND OF THE INVENTION

The present invention generally relates to vacuum filter devices andparticularly to such devices for filtering liquids from one containerthrough a membrane and depositing the filtrate directly into anothercontainer. More particularly, the invention relates to a liquid-tightfiltration system in which solutions, such as tissue culture anedia, arevacuum filtered.

Devices for filtering biological solutions generally involve threeprimary components, i.e. a membrane filter interposed between twovessels, a feed container located upstream of the membrane for holdingthe sample solution to be filtered and a filtrate container locateddownstream of the membrane filter for collecting the filtered samplesolution. Often a vacuum is drawn downstream of the membrane to increasethe rate of filtration by creating a pressure differential across thefilter. However, in such cases provisions must be made to maintain thepressure differential across the membrane and thus assuring that thefiltration will not stop.

The arrangement of components for vacuum filtration can take variousforms; however, especially in laboratory settings, ease of use, reducedstorage requirements and minimal disposable hardware are importantconcerns as is avoiding spillage of the biological solution. In certainother applications, preserving the sterility of the solution beingfiltered is also important.

An example of a vacuum filter device is described in U.S. Pat. No.4,673,501 wherein an open funnel for receiving a sample of solution tobe filtered is arranged to be sealed to the top of a bottle forcollecting filtrate. The base of the funnel includes a membrane filterpositioned such that when the sample to be filtered is poured into thetop of the funnel all of the sample solution is directed to flow throughthe membrane filter. A vacuum conduit which is adapted to be connectedto a vacuum source is formed within the base of the funnel and allows avacuum to be drawn within the filtrate bottle thereby drawing the samplesolution through the membrane filter. Since the pressure differentialacross the filter is constant due to the application of a vacuum on thedownstream side of the filter and atmospheric pressure present on theliquid surface of the open funnel, rapid filtration is possible and anyreduction in flow rate is clue to filter fouling. Nonetheless, vacuumfilter devices of the type described in this patent suffer from a numberof drawbacks which make them inconvenient for laboratory use. First,these devices require the liquid sample be transferred from its normallaboratory container to an open funnel. Because of the liquid weightconcentrated at the top of this assembly, they are prone to tipping andhence spilling the biological solution during pouring of sample or whenconnecting hoses. Aside from the inconvenience to the user in handlingthe fluid to be filtered, there is an enhanced risk of compromising thesterility of the particular biological solution due to the open natureof this device. Moreover, the large size of these filter assembliesresults in their taking up limited laboratory storage space. Inaddition, since the containers utilized in the filtration process aredisposable and intended for one-time use, a significant amount of solidwaste is generated by these filter assemblies and the associated pre-and post- filtration containers.

To minimize the amount of solid waste and fluid transfers, U.S. Pat. No.5,141,639 describes a vacuum filter assembly wherein the membrane filteris disposed in a cover sealable to the filtrate container. The cover isformed with a feed port in the form of a tubular feed nipple on theupstream side of the membrane filter. A length of tubing is connected atone end to the feed nipple and the other end is directly inserted into asample container housing the solution to be filtered. The cover alsoincludes a filtrate outlet port and a vacuum port, both of whichfluidically connect with the downstream side of the membrane filter.When tubing is attached to the vacuum port and a vacuum is drawn thesample solution to be filtered is caused to flow through the tubing andpass through the membrane filter to the filtrate container. As is thecase with the aforementioned U.S. Pat. No. 4,673,501, the pressuredifference in this prior art assembly remains constant because of thevacuum in the filtrate container and the atmospheric pressure acting onthe liquid surface in the open feed or sample container. While thisdevice minimizes the amount of solid waste generated during filtration,it is cumbersome to use as the operator must assemble the tubing to thecover and hold the over on the filtrate container until the necessaryvacuum pressure has been achieved in the filtrate container.Additionally, the feed tubing must be maintained submerged in the samplecontainer to avoid air being drawn into the sample solution which coulddisrupt the filtration. In addition, the sample is housed in an opencontainer; therefore, the risk of compromising sterility is heightened.

Thus it is apparent that the need still exists for an improved vacuumfilter device that is easy to use, reduces the solid waste generated,minimizes the number of times the fluid is transferred and reduces therisk of liquid spillage.

SUMMARY OF THE INVENTION

The present invention overcomes the disadvantages and limitations of theprior art by providing a vacuum filter device for filtering solutionswhich includes a filter body having two junctions disposed on oppositesides of a filter. Each junction is adapted to receive a closedcontainer in a fluid-tight, sealed relationship. Other aspects of theinvention include provisions for forming a substantially liquid-tightfiltration system and for reducing the risk of contaminating the samplesolution to be filtered. The invention also minimizes the risk ofspillage and contamination of the solution by eliminating fluid transferbetween open containers. The device also includes a vacuum portcommunicating with the downstream side of the filter, and hence thefiltrate container. When connected to a vacuum source, the pressuredifferential will allow a vacuum to draw the sample solution from thesample container through the filter and into the filtrate container. Tomaintain the pressure differential necessary to continue the flow ofsample, a passageway communicates with the upstream side of themembrane, and hence the sample container, to provide a vent toatmospheric pressure.

In accordance with a preferred embodiment of the invention, twoidentical laboratory containers, for example centrifuge tubes, arescrewed onto opposite sides of a filter body. The filter body has twomating threaded recesses disposed along the central axis of the body,with each recess having a raised annular ring for creating a fluid-tightseal with the top of the container when it is screwed into the body. Theportion of the filter body between the two recesses includes a membranefilter bonded to a suitable support. Two passageways formed in thefilter body communicate fluidically with the opposite sides of themembrane and ultimately with each of the containers. One of thepassageways is a vacuum port which communicates with the downstream sideof the membrane and is adapted to be connected to a vacuum source forenabling sample to be drawn through the membrane filter and be collectedas filtrate. The other passageway communicates with the upstream side ofthe membrane (and the sample container) and serves as a vent toatmospheric pressure.

When a sample solution is placed in the sample container and both thesample container and an empty filtrate container are secured to thefilter body, a vacuum is applied to the vacuum port to create a pressuredifferential between the two containers. This pressure differentialcauses sample fluid to pass through the membrane filter from the samplecontainer to the filtrate container. As the volume of fluid in thesample container is reduced, air enters through the venting passagewayto maintain the pressure differential across the membrane so thatfiltration continues uninterrupted until all the ample is filtered.

In accordance with one aspect of the invention particularly suitable forapplications where leaking of the solution is of concern, the ventingpassageway is less than 0.015 inches in its smallest dimension. Thispassageway is made by inserting a forming tool between the two halves ofthe filter body prior to the integral joining process. Once the twohalves have been joined, the forming tool is removed and a passagewaybetween the halves of the body is formed having dimensions correspondingto that of the forming tool. The creation of such a small dimensionpassageway, heretofore unattainable through conventional molding andassembly techniques, allows it to be used in the filter device of thepresent invention as a venting passageway without incorporating anyother structure such as a membrane covering the passageway to preventsolution from leaking out of the filtration system during normal use.For purposes herein normal use includes transporting containers withinthe laboratory and tipping containers either during use or while beingtransported.

In certain applications, the liquid-tight feature of the above mentionedsmall dimension passageway is enhanced by decreasing the surface energyof the passageway. This may be achieved by either inserting ahydrophobic liner into the passageway or applying a hydrophobic surfacetreatment to all or a portion of the internal surfaces of thepassageway.

These and other aspects and advantages of the invention will becomeapparent from the following detailed description taken in conjunctionwith the drawings.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front elevation view of a preferred embodiment of a vacuumfilter device with laboratory containers coupled thereto in accordancewith the invention;

FIG. 2 is a detailed sectional view of the filter body of the device ofFIG. 1;

FIG. 3 is an exploded view of the filter body illustrating the assemblyof the membrane filter;

FIG. 4A is an enlarged sectional view of one embodiment of the ventingpassageway of the filter body of FIG. 2;

FIG. 4B is an enlarged sectional view of another embodiment of theventing passageway of the filter body of FIG. 2;

FIGS. 5A, B and C are a series of diagrammatic views illustrating theprocess of forming the venting passageway in the device of FIG. 1;

FIG. 6 is a sectional view of an alternate embodiment of a vacuum filterdevice in accordance with the invention;

FIG. 7 is a sectional view of still another alternate embodiment of avacuum filter device in accordance with the invention, and

FIG. 8 is a sectional view of yet another alternate embodiment of avacuum filter device in accordance with the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 shows a vacuum filter device 10 which includes a filter bodygenerally indicated by numeral 11 having a pair of axially disposedtubular holders 12, 13 each having a threaded open end. The holders arebonded back-to-back (see also FIG. 3) at interface 14 by any suitablewelding technique such as ultrasonic welding to form an integral body.The open end of the holders serve as a junction to accept a closedsample container 15 for a biological fluid such as tissue culture mediato be filtered and a closed filtrate container 16 for collecting thefiltered sample (filtrate).

The holder 13 includes a face plate 17 with a series of radiallyextending ribs 19 molded on the top surface of the plate which act as asupport for a porous membrane 18 which is welded at its periphery to theplate 17 prior to bonding the two holders together. For applicationsinvolving the sterile filtration of tissue culture media, a particularlysuitable microporous membrane is a 0.22 micron polyethersulfone membraneavailable from Millipore Corporation under the brand name Express™.However, depending on the filtration application, the membrane may bemade from any other suitable polymeric materials such as mixed esters ofcellulose, cellulose acetate, polycarbonate, polyvinylidene fluoride,polytetrafluoroethylene, nylon, polypropylene, polyethylene or the like.The use of inorganic materials is also possible as well as filterstructures that are not microporous (e.g. depth filters). In someapplications, a combination of filters may provide improved performance.For example, for particularly dirty samples a depth filter 80 (see FIG.8) which functions as a prefilter matrix in combination with amicroporous membrane filter can be used.

Referring also to FIG. 2, the bottom of the holder 12 which abuts theface plate 17 includes a membrane guard 20 formed as part of the holder.The guard is wagon-wheeled shaped such that when the two holders 12, 13are bonded together sample solution can flow through a series ofopenings 21 and then be filtered by the membrane 18. A passageway 30provides the fluid communication link between the downstream side of themembrane 18 and the filtrate container 16.

The filter body 11 has respective raised annular rings 22A, 22B whichare molded within each of the holders 12, 13 near to their periphery. Avacuum port 23 in communication with the downstream side of the membrane18 includes a filter matrix 24 within the central bore of the port 23.The matrix 24 is used to prevent the migration of contaminants such asbacteria or oil residues from entering the filtrate during vacuumoperation as well as to protect the vacuum system from beingcontaminated by the filtered sample. A tube adapter 26 is secured to thevacuum port. A venting passageway 25, the details of which are bestshown in FIGS. 4A and 4B, is formed at the interface 14 of the twoholders and is in fluid communication with the upstream side of themembrane and provides a vent for the sample container 15.

The inclusion of the venting passageway 25 is important to the properoperation of the vacuum filter device 10 because the sample container 15is a closed vessel and the overall filter device is of liquid-tightconstruction. The venting passageway allows for maintaining thenecessary pressure differential across the filter, a feature attributedto the previously described prior art because of the open nature oftheir feed containers at a sacrifice of the benefits of the liquid-tightsystem of the present embodiment, such as minimizing the risk of sic,ills and contamination. While a closed sample container would be able tostart the filtration process, it would not provide commerciallyacceptable performance over the course of filtration. To explain, theclosed sample container starts the filtration process with an internalstarting pressure at atmospheric pressure. As vacuum is applied to thevacuum port 23, the pressure differential (ΔP) across the membrane isdefined by ΔP=(P_(sample) -P_(filtrate)) where P_(sample) is the airpressure in the sample container and P_(filtrate) is the air pressure inthe filtrate container. Initially, P_(sample) =P_(filtrate)=P_(atmosphere) ; however, as fluid is drawn through the membrane 18 tothe filtrate container 16 the sample volume is being reduced. In aclosed system, this reduction in the amount of sample in the samplecontainer over time t1 to t2 translates to a reduction in pressure, asgoverned by the pressure/volume relationship (P_(sample)(t1)V_(sample)(t1) =P_(sample)(t2) V_(sample)(t2)) where P_(sample) andV_(sample) relate to the gas within the sample container. As thepressure in the sample container is reduced, the ΔP is lessened therebyslowing the flow rate. If allowed to continue P_(sample) will equalP_(filtrate) resulting in no flow. To insure the maximum ΔP and hencethe greatest flow rate, the sample container needs to be maintained asclose to P_(atmosphere) as possible. With the present invention, thisgoal is achieved by the venting passageway connecting the samplecontainer with the outside atmospheric pressure.

In accordance with an important aspect of the invention involvingsubstantially liquid-tight filtration applications, the ventingpassageway as shown in FIG. 4A is formed in the filter body in a mannerwhich creates a passageway whose smallest dimension is 0.015 inches orless. Details of the techniques used to create this small dimensionpassageway in the filter body 11 are best discussed with reference toFIGS. 5A, B and C. As discussed, the filter body is constructed byultrasonically welding the two holders 12, 13 at the interface 14. Asshown in FIG. 5A, a forming tool 50 is placed between the two holdersprior to initiating the weld process. This tool can take a variety ofshapes depending on the desired dimensions of the orifice. In thisembodiment a circular wire of diameter 0.015 inches is used, although itwill be understood that forms of rectangular cross-section or even othergeometries may be employed. FIG. 5B shows the holders placed togetherwith the forming tool in position as ultrasonic energy is applied. Afterthe holders are welded together, the forming tool is removed leaving athrough-hole whose dimensions correspond to that of the tool. To assistin the removal, the remote end of the forming tool can be slightlytapered such that as the minimum force required to begin disengaging theforming tool is applied the remainder of the tool will more readily beremoved from the interface 14 between the two holders.

Injection molding methods generally provide the greatest dimensionalcontrol of shape with plastic parts. To apply conventional moldingtechniques in the present instance, it would be desirable to mold apassageway in the wall section of the filter body 11 remote from thejoining surfaces of the two holders 12, 13 in order to eliminate thedeformation of the passageway during assembly thereby retaining thedimensional control. However, conventional molding processing techniqueswould not allow a passageway that is molded into the wall of the holder12 to be 0.015 inches or less. This is because as the molten plasticenters the mold cavity the pin used to create the passageway woulddeflect leading to fatigue and breakage. Also, for the pin to seal offagainst the other wall of the cavity, the sealing end of the pin will bepeeled over in time leading to flashing. Flashing is an uncontrollable,undesirable migration of plastic, which in this example will lead tofilling and dimensionally distorting the venting passageway 25.

If, instead of molding a passageway in the wall of the filter body 11 asdiscussed above, an attempt were made to mold an interruption or notchon the joining surfaces of the holders 12, 13 with dimensions of 0.015inches or less, the joining process, whether it be vibrational, thermalor chemical, would distort or even close the passageway because the twosurfaces are joined by softening and moving the plastic togetherfollowed by a stabilization period. The plastic that moves duringjoining will be squeezed into available areas, such as the void createdby the molded in interruption. Also the direction of movement of theplastic during the joining process is not controllable. Thus as theplastic moves into the interruption it will dimensionally change theshape and possibly close the interruption altogether.

The use of a forming tool during the joining process provides for adimensionally controlled geometry that is independent of the moldingprocess and controllable with a variety of joining processes in additionto the ultrasonic welding process of the embodiment described, such asvibration bonding, radiant heat and other fusion bonding processes aswell as solvent bonding.

The ability to form the venting passageway 25 with dimensions of 0.015inches or less provides significant advantages in that the filtrationdevice maintains its liquid-tight capabilities without employing anadditional membrane covering the venting passageway to prevent solutionfrom leaking out of the device during normal use.

In some applications where the solution to be filtered has low surfacetension which allows the solution to readily wet surfaces, such assolutions containing surfactants, it may be advantageous to imparthydrophobic properties to all or a portion of the venting passageway 25.One way to maintain the liquid-tight attributes of the present inventionin such applications is to decrease the surface energy of thepassageway. FIG. 4B shows the inclusion of a hydrophobic liner 44positioned in the venting passageway 25 which serves as a hydrophobicporous matrix. Preferred forms of this matrix include porous hollowfiber membranes, porous polymer rods or microbore tubing, allconstructed from a suitable hydrophobic resin. To fabricate the filterbody 11 with the liner 44, a molded slot of predetermined dimension andgeometry sufficient to encapsulate the liner is formed in opposingsurfaces 45, 46 of the respective holders 12, 13. The liner is thencrimped in place without collapsing its lumen during the holder joiningprocess to provide fluid communication between the sample container 15and the outside atmospheric pressure. Use of a hydrophobic liner allowsthe materials of the filter body to be selected based on economics orspecific material properties. As mentioned, the venting passageway neednot be completely lined but only imparted with hydrophobic propertiesalong a portion of the passageway.

Since the liquid-tight characteristic of the present invention isenhanced when the small dimension venting passage 25 described inaccordance with the embodiment of FIG. 4A is utilized, this attributemay be further enhanced by applying a hydrophobic treatment to thesurfaces of the passageway, preferably in liquid form during assembly ofthe FIG. 4A embodiment. A hydrophobic solution such aspolytetrafluoroethylene (PTFE) in suspension may be applied to theforming tool 50 before the tool is inserted between the holders 12, 13.When the tool is removed after weld energy is applied, a film of thePTFE remains on the inner surfaces of the venting passageway. Thehydrophobic liquid treatment decreases the surface energy and preventsleakage of the sample solution during normal laboratory use.

In operation, a sample solution to be filtered is deposited in thesample container 15 and is screwed tightly onto the holder 12 with theopen end of the sample container being held upward until the upper lipof the container is squeezed against the angled surface of the ring 22A.Tightly screwing the container to the filter body 11 creates afluid-tight seal. In similar fashion, the filtrate container 16 isscrewed into the holder 13 against the angled surface of the ring 22B.Optionally, an elastomeric gasket 55 (see FIG. 8) may be positionedwithin the base of the holders 12, 13 to provide the necessary seal. Forsterile filtration of tissue culture, the filtrate container and thefilter body are pre-sterilized prior to coupling them together.

The device 10 is then flipped over such that the sample container 15 isoriented upward with respect to the filter body 11 as shown in FIG. 1. Alength of tubing 28 is connected to a vacuum pump (not shown) and avacuum is applied to port 23 and the filtrate container is evacuated ofair and the pressure therein correspondingly reduced. The unfilteredsample solution is then passed from the higher pressure sample container15 through the membrane guard 20 and the membrane 18. The filteredsolution flows through the opening 30 and collects as filtrate in thefiltrate container 16. To maintain the pressure differential, whichserves as a driving force, air at atmospheric pressure enters throughthe venting passageway 25 and replaces the volume of sample solutionthat passes through the membrane. The dimensions of the ventingpassageway discussed with respect to the embodiment shown in FIG. 4A areso small that sample does not leak out from the sample container 15,thus preserving the liquid-tight nature of the filtration device.

FIG. 6 shows an alternate embodiment of the device 10 wherein likenumerals refer to the same elements as those shown in FIG. 1. Theconstruction and operation is similar to the FIG. 1 embodiment exceptthe vent for the sample container 15 is a passageway 60 whose dimensionsare compatible with those derived from conventional molding techniques(i.e. >0.015 inches). In this instance a hydrophobic membrane 62 coversthe opening of the passageway 60 to keep sample solution from spillingout of as well as preventing microbes from entering the container 15.Thus when used with a sterilizing grade filter such as theaforementioned Express™ membrane, the filtration system of thisembodiment represents a sterile, closed system which maintains thesterility of the solutions being processed.

FIG. 7 shows still another embodiment similar to that of the FIG. 6embodiment except that no vent membrane is used to cover passageway 70.Instead the membrane 18 includes both a hydrophilic region 71 whichseparates the two closed containers 15, 16 and a hydrophobic region 72which is in direct fluid communication with the passageway 70. In thisinstance the membrane is also sealed to the face plate 17 at bondingpoint 73 in the vicinity of the interface between the hydrophilic andhydrophobic regions. To assure that the hydrophobic region forms anintegral seal with the passageway, the membrane seal at point 73 muststraddle both the hydrophilic and hydrophobic regions. As vacuum isdrawn through the port 23, the sample solution will flow through thehydrophilic region of the membrane. At the same time air enters thepassageway 70 and ultimately passes into the sample container 15 throughthe hydrophobic region of the membrane. This embodiment thus presentsthe same attributes of liquid-tight and sterile sealed filtration asthat of the embodiment shown in FIG. 6.

FIG. 8 shows yet another embodiment of the invention similar to that ofthe FIG. 2 embodiment. In this embodiment, sealing is achieved throughthe elastomeric gasket 55 instead of the rings 22A, 22B. Also shown isthe depth filter 80 in combination with the membrane 18. This depthfilter functions as a prefilter matrix for the filtration device.

We claim:
 1. A vacuum filter device comprising:a single filter bodyhaving two holders disposed from one another, each of said holdersadapted to receive respective feed and filtrate containers; each of saidholders including sealing means for creating a liquid and air tight sealwhen said containers are coupled to said filter body, said feedcontainer for housing a liquid to be filtered and said filtratecontainer for receiving the filtered liquid, each of said containersforming liquid tight receptacles when coupled to said filter body; afilter sealed within said filter body between said holders so thatliquid in said feed container must pass through said filter prior toentering said filtrate container; a vacuum port extending through saidfilter body and being in fluid communication with said filtratecontainer at a downstream side of said filter, said vacuum port adaptedto be connected to a vacuum source for drawing said liquid from saidfeed container through said filter and into said filtrate container; anda vent passageway in said filter body configured to permit gas in theatmosphere surrounding said vacuum filter device to be in direct fluidcommunication with said feed container on an upstream side of saidfilter and not to be in direct fluid communication with said filtratecontainer.
 2. The device of claim 1 wherein said filter body is ofcircular cross-section and said vent passageway extends through saidfilter body radially inward from the periphery of said filter body. 3.The device of claim 2 wherein said vent passageway is of circularcross-section and has a diameter of 0.015 inches or less.
 4. The deviceof claim 2 wherein said vent passageway is of rectangular cross-sectionand the smallest dimension of said passageway is 0.015 inches or less.5. The device of claim 1 wherein said filter is a microporous membrane.6. The device of claim 1 wherein said filter is a depth filter.
 7. Thedevice of claim 1 wherein said filter is a combination of a microporousmembrane and a depth filter.
 8. The device of claim 1 including ahydrophobic membrane integrally sealing said vent passageway.
 9. Thedevice of claim 1 including a hydrophobic porous matrix positionedwithin said vent passageway.
 10. The device of claim 1 including ahydrophobic tube positioned within said vent passageway.
 11. The deviceof claim 1 wherein at least a portion of the surfaces of said ventpassageway is hydrophobic.
 12. The device of claim 1 wherein said filteris a microporous membrane which is segmented into hydrophilic andhydrophobic regions.
 13. The device of claim 12 wherein said hydrophilicregion separates said feed and filtrate containers and said hydrophobicregion integrally seals said vent passageway.
 14. The device of claim 1wherein said filter body is of circular cross-section, said junctionsare threaded holders axially disposed from each other and said andfiltrate containers having mating threads for engaging said recess. 15.The device of claim 14 wherein said sealing means comprises a raisedannular ring adapted to engage said feed and filtrate containers to forma compressive fit between said ring and the wall of said holders whensaid feed and filtrate containers are threaded therein.
 16. The deviceof claim 14 wherein said sealing means comprises an elastomeric gasketpositioned within the base of said holders.
 17. The device of claim 1including a prefilter matrix disposed upstream of said filter.